The expansive goal of this project is to develop new means to visualize the activation of endogenous voltage gated ion channels (VGICs). Difficulties in identifying when and where specific VGICs become involved in electrical signals limit our fundamental understanding of neuronal circuits and impede the discovery of therapeutics. Novel tools to image the activity of VGIC subtypes enable fluorescence imaging of channel participation in physiological and pathophysiological signaling. Technology to see specific ion channels activate could aid in validation of drug targets for a host of maladies, including chronic itch and neuropathic pain. Neurons exhibit tremendous diversity in their electrical signaling, a consequence of the distinct collections of VGICs different cells. Understanding how individual VGIC subtypes contribute to electrical signaling remains a significant challenge. We propose to develop ion channel activity probes to monitor activity of VGICs in neurons. This technology we are developing can, in principle, be used to target any subtype of VGIC.